VARIABILITY OF DIPHENHYDRAMINE N-GLUCURONIDATION IN HEALTHY-SUBJECTS

The H-1-antagonist diphenhydramine can undergo direct glucuronidation at its tertiary amino group with formation of a quaternary ammonium gl ucuronide. The intraindividual variability in the amount of N-glucuron ide excretion in urine was investigated in two female volunteers who r epeatedly took single doses of 25 mg diphenhydramine hydrochloride wit hout and with concomitant administration of ascorbic acid or ammonium chloride for urine acidification. Another two female and four male sub jects underwent single tests without and with additional ascorbic acid . Diphenhydramine N-glucuronide quantities in urine differed significa ntly among subjects and ranged between 2.7% and 14.8% of the dose with in 8 h. Neither ascorbic acid nor ammonium chloride significantly infl uenced the quantity of N-glucuronide in urine, but ammonium chloride, that in contrast to ascorbic acid proved effective in lowering urinary pH, increased the excretion of the parent drug.